rs41284066

Positions:

• chr10-80280367-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000372213.8(MAT1A):​c.406-51C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0488 in 1,607,964 control chromosomes in the GnomAD database, including 2,196 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.054 (211 hom., cov: 31)
  • Exomes 𝑓: 0.048 (1985 hom.)
• Consequence: MAT1A ENST00000372213.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.347

Genes affected

MAT1A (HGNC:6903): (methionine adenosyltransferase 1A) This gene catalyzes a two-step reaction that involves the transfer of the adenosyl moiety of ATP to methionine to form S-adenosylmethionine and tripolyphosphate, which is subsequently cleaved to PPi and Pi. S-adenosylmethionine is the source of methyl groups for most biological methylations. The encoded protein is found as a homotetramer (MAT I) or a homodimer (MAT III) whereas a third form, MAT II (gamma), is encoded by the MAT2A gene. Mutations in this gene are associated with methionine adenosyltransferase deficiency. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 10-80280367-G-A is Benign according to our data. Variant chr10-80280367-G-A is described in ClinVar as [Benign]. Clinvar id is 1178402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAT1A	NM_000429.3	c.406-51C>T		intron_variant		ENST00000372213.8	NP_000420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAT1A	ENST00000372213.8	c.406-51C>T		intron_variant		1	NM_000429.3	ENSP00000361287	P1
MAT1A	ENST00000455001.1	c.217-51C>T		intron_variant		5		ENSP00000414961

Frequencies

GnomAD3 genomes AF: 0.0540 AC: 8211 AN: 151968 Hom.: 210 Cov.: 31

Gnomad AFR AF: 0.0611

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0399

Gnomad ASJ AF: 0.0896

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0399

Gnomad FIN AF: 0.0613

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0552

Gnomad OTH AF: 0.0412

GnomAD3 exomes AF: 0.0475 AC: 11728 AN: 246698 Hom.: 357 AF XY: 0.0488 AC XY: 6520 AN XY: 133600

Gnomad AFR exome AF: 0.0594

Gnomad AMR exome AF: 0.0233

Gnomad ASJ exome AF: 0.0974

Gnomad EAS exome AF: 0.000547

Gnomad SAS exome AF: 0.0457

Gnomad FIN exome AF: 0.0611

Gnomad NFE exome AF: 0.0545

Gnomad OTH exome AF: 0.0502

GnomAD4 exome AF: 0.0482 AC: 70220 AN: 1455878 Hom.: 1985 Cov.: 35 AF XY: 0.0487 AC XY: 35260 AN XY: 724444

Gnomad4 AFR exome AF: 0.0622

Gnomad4 AMR exome AF: 0.0244

Gnomad4 ASJ exome AF: 0.0971

Gnomad4 EAS exome AF: 0.000353

Gnomad4 SAS exome AF: 0.0449

Gnomad4 FIN exome AF: 0.0593

Gnomad4 NFE exome AF: 0.0490

Gnomad4 OTH exome AF: 0.0486

GnomAD4 genome AF: 0.0539 AC: 8205 AN: 152086 Hom.: 211 Cov.: 31 AF XY: 0.0541 AC XY: 4022 AN XY: 74358

Gnomad4 AFR AF: 0.0611

Gnomad4 AMR AF: 0.0398

Gnomad4 ASJ AF: 0.0896

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0389

Gnomad4 FIN AF: 0.0613

Gnomad4 NFE AF: 0.0552

Gnomad4 OTH AF: 0.0403

Alfa AF: 0.0663 Hom.: 64

Bravo AF: 0.0508

Asia WGS AF: 0.0220 AC: 75 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 14, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs41284066; hg19: chr10-82040123;